Pragmatic MRD-guided maintenance after allo-HCT; no single drug target

This prospective, open-label pragmatic study from the Medical College of Wisconsin tests whether using pre-transplant measurable residual disease (MRD) status to assign post–allogeneic hematopoietic cell transplant (allo-HCT) maintenance therapy can reduce relapse in myeloid malignancies. Patients undergo “usual” pre-HCT MRD testing (immunophenotypic flow and/or molecular assays), then are assigned by MRD: MRD-positive participants start physician-selected maintenance therapy, while MRD-negative participants receive no maintenance intervention. The intervention is intentionally flexible (choice of maintenance at the treating physician’s discretion), so there is no single study drug and therefore no single mechanism of action/target to summarize; instead, the trial evaluates the strategy of MRD-guided escalation vs observation. The key angle is real-world implementability: it mirrors how transplant centers already individualize post-HCT management, but formalizes it prospectively. Today’s post-allo-HCT approach for many myeloid malignancies is close monitoring (labs, marrow checks, MRD when available) with tapering immunosuppression and/or pre-emptive therapy when relapse risk is high, plus targeted maintenance in selected molecular subsets (e.g., FLT3 inhibitors in FLT3-ITD AML).